Human Immunodeficiency Virus Type 1 (HIV-1)- and Epstein-Barr Virus-Specific Cytotoxic T Lymphocyte Precursors Exhibit Different Kinetics in HIV-1-Infected Persons

Geretti, Anna María; Dings, Marlinda E. M.; van, Cécile A. C. M.; Baalen, Carel A. van; Wijnholds, Folko J.; Borleffs, Jan C. C.; Osterhaus, Albert D. M. E.

doi:10.1093/infdis/174.1.34

Cited by 31 publications

(13 citation statements)

References 40 publications

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“…Human B-lymphoblastoid cell lines (B-LCL) were generated from peripheral blood mononuclear cells purified by standard Ficoll (Biochrom, Berlin, Germany) density centrifugation according to a previously described method (4). MVA-gfp was constructed as previously described (16).…”

Section: Methodsmentioning

confidence: 99%

Neutralization Assay Using a Modified Vaccinia Virus Ankara Vector Expressing the Green Fluorescent Protein Is a High-Throughput Method To Monitor the Humoral Immune Response against Vaccinia Virus

Cosma

Bühler

Nagaraj

et al. 2004

Clin Vaccine Immunol

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Vaccination against smallpox is again considered in order to face a possible bioterrorist threat, but the nature and the level of the immune response needed to protect a person from smallpox after vaccination are not totally understood. Therefore, simple, rapid, and accurate assays to evaluate the immune response to vaccinia virus need to be developed. Neutralization assays are usually considered good predictors of vaccine efficacy and more informative with regard to protection than binding assays. Currently, the presence of neutralizing antibodies to vaccinia virus is measured using a plaque reduction neutralization test, but this method is time-consuming and labor-intensive and has a subjective readout. Here, we describe an innovative neutralization assay based on a modified vaccinia virus Ankara (MVA) vector expressing the green fluorescent protein (MVA-gfp). This MVA-gfp neutralization assay is rapid and sensitive and has a high-throughput potential. Thus, it is suitable to monitor the immune response and eventually the efficacy of a large campaign of vaccination against smallpox and to study the vector-specific immune response in clinical trials that use genetically engineered vaccinia viruses. Most importantly, application of the highly attenuated MVA eliminates the safety concern in using the replication-competent vaccinia virus in the standard clinical laboratory.

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Section: Methodsmentioning

confidence: 99%

Neutralization Assay Using a Modified Vaccinia Virus Ankara Vector Expressing the Green Fluorescent Protein Is a High-Throughput Method To Monitor the Humoral Immune Response against Vaccinia Virus

Cosma

Bühler

Nagaraj

et al. 2004

Clin Vaccine Immunol

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“…For example, there is an HLA-A25 restricted CTL epitope, (ETINEEAAEW) that has been defined using CTL. clones from long term survivors [van Baalen (1996)l. This epitope is conserved in viruses of the B and D subtypes, but the form DTINEEAAEW is commonly in other clades, and this variant was not recognized by CTL specific for the index peptide.…”

Section: Additional Immunogenic Domains In P24mentioning

confidence: 99%

Human retroviruses and AIDS 1996. A compilation and analysis of nucleic acid and amino acid sequences

Myers¹,

Foley²,

Korber

et al. 1997

366

678

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“…Zajac and colleagues also showed that the silent phenotype of virus-specific CTL was especially prevalent when there was inadequate CD4 help. Infection with SIV or HIV does impair CD4 help (5,12,21,24), and it may therefore not only result in a loss of virus-specific CD8 T-cell response over time (8,15) but also result in a functional impairment of the virus-specific CTL response. Although the absolute numbers of CD4-positive cells per microliter of blood in our SIV-infected monkeys were continuously decreasing over time (data not shown), there was no obvious correlation between the drop in IFN-␥ production in tetramer-positive cells with CD4 counts.…”

Section: Functionally Impaired Cd8mentioning

confidence: 99%

Functional Impairment of Simian Immunodeficiency Virus-Specific CD8⁺T Cells during the Chronic Phase of Infection

Vogel

Allen

Altman

et al. 2001

J Virol

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In an attempt to determine why high frequencies of circulating virus-specific CD8 ؉ T cells are unable to control human immunodeficiency virus and simian immunodeficiency virus (SIV) replication, we assessed the functional nature of SIV-specific CD8 ؉ lymphocytes. After vaccination and early after infection, nearly all tetramer-staining CD8؉ cells produced gamma interferon in response to their specific stimulus. However, by 4 months postinfection with pathogenic SIVmac239, signs of functional impairment in the CD8 ؉ T-cell compartment were detected which might prevent these T cells from efficiently controlling the infection during the chronic phase.It is still unclear why the immune system is not able to clear an infection with immunodeficiency viruses. These lentiviruses appear to have devised multiple strategies to evade the immune response (reviewed in reference 26), including major histocompatibility complex class I downregulation (10) and escape from cytotoxic T lymphocyte (CTL) responses (1,7,9,13,17,27). However, the maintenance of high frequencies of virus-specific cells against certain viral epitopes in human immunodeficiency virus (HIV)-infected humans (4, 23, 30) and simian immunodeficiency virus (SIV)-infected monkeys (19,20) indicates that these epitopes are still being recognized and have not mutated. While the invention of tetramers (4) made it possible to detect these high frequencies of virus-specific cells in HIV and SIV infection, tetramer staining simply identifies antigen-specific lymphocytes but does not provide information about the functional nature of these virus-specific cells. Functionally impaired CD8ϩ T-cell responses have been previously described by Zajac et al. in chronic lymphocytic choriomeningitis virus (LCMV) infection (31) and by Lee et al. in a tumor system (22), where CTL were unable to directly lyse their specific target cells and produce cytokines in response to mitogens. We therefore were interested in investigating whether similar functional defects could account for the inability of CD8 ϩ T cells to control HIV and SIV infections. To address this question we combined tetramer-staining technology (4) and the intracellular cytokine assay (18, 25) to determine whether SIV-specific CD8 ϩ T cells manifest any functional defects.The majority of tetramer-positive cells produce IFN-␥ after peptide-specific stimulation in vaccinated animals and early after infection with pathogenic SIVmac239. Using an epitopebased DNA prime-modified vaccinia virus Ankara boost vaccine, we induced Mamu-A*01-restricted, p11C,C-M (CM9)-specific CTL (2) in three Mamu-A*01-positive rhesus macaques (95058, 95045, and 96031), as previously described (3). We followed the levels of Mamu-A*01/CM9-specific cells in these animals before and after intrarectal infection with SIVmac239 (molecular clone) by tetramer staining and investigated their ability to produce gamma interferon (IFN-␥) after antigen-specific stimulation using the intracellular cytokine assay. Fresh or thawed peripheral blood mononuclear c...

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Human Immunodeficiency Virus Type 1 (HIV-1)- and Epstein-Barr Virus-Specific Cytotoxic T Lymphocyte Precursors Exhibit Different Kinetics in HIV-1-Infected Persons

Cited by 31 publications

References 40 publications

Neutralization Assay Using a Modified Vaccinia Virus Ankara Vector Expressing the Green Fluorescent Protein Is a High-Throughput Method To Monitor the Humoral Immune Response against Vaccinia Virus

Neutralization Assay Using a Modified Vaccinia Virus Ankara Vector Expressing the Green Fluorescent Protein Is a High-Throughput Method To Monitor the Humoral Immune Response against Vaccinia Virus

Human retroviruses and AIDS 1996. A compilation and analysis of nucleic acid and amino acid sequences

Functional Impairment of Simian Immunodeficiency Virus-Specific CD8⁺T Cells during the Chronic Phase of Infection

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Human Immunodeficiency Virus Type 1 (HIV-1)- and Epstein-Barr Virus-Specific Cytotoxic T Lymphocyte Precursors Exhibit Different Kinetics in HIV-1-Infected Persons

Cited by 31 publications

References 40 publications

Neutralization Assay Using a Modified Vaccinia Virus Ankara Vector Expressing the Green Fluorescent Protein Is a High-Throughput Method To Monitor the Humoral Immune Response against Vaccinia Virus

Neutralization Assay Using a Modified Vaccinia Virus Ankara Vector Expressing the Green Fluorescent Protein Is a High-Throughput Method To Monitor the Humoral Immune Response against Vaccinia Virus

Human retroviruses and AIDS 1996. A compilation and analysis of nucleic acid and amino acid sequences

Functional Impairment of Simian Immunodeficiency Virus-Specific CD8+T Cells during the Chronic Phase of Infection

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Functional Impairment of Simian Immunodeficiency Virus-Specific CD8⁺T Cells during the Chronic Phase of Infection